Behavioral contingencies modulate tolerance to discriminative stimulus effects of morphine

Experiments examined how learning processes modulate tolerance to discriminative stimulus effects of morphine. Rats were trained to discriminate saline and 3.2 mg/kg morphine, and the doses of morphine required to mimic the training dose were determined before, during and after repeated treatment with saline or high doses of morphine (10 mg/kg, b.i.d.). In one set of experiments, training was either suspended or continued with saline and the original training dose during a 2-week treatment regimen. When training was suspended, high-dose morphine treatment increased the dose of morphine required for stimulus effects approximately 3-fold. Tolerance persisted 2 days after treatment ended, but disappeared within 7 days. In contrast, continued training with saline and 3.2 mg/kg morphine during high-dose treatment both attenuated development of tolerance and transferred control to lower doses. Transfer of control to lower doses appeared conditional upon recent termination of high-dose treatment, as it disappeared within 7 days. Treatment with saline did not change the doses of morphine required for stimulus effects under either training condition. A final experiment examined whether high-dose treatment could transfer control to higher doses of morphine. The treatment dose of 10 mg/kg morphine itself was used as the training dose during a 2-week treatment regimen. The dose of morphine required for stimulus effects increased 2- to 4-fold during treatment, but quickly returned to control values when treatment ended. These results extend previous findings that conditioning and pharmacodynamic processes jointly regulate development of tolerance to discriminative effects of morphine.     

Renal hemodynamics in the rat before and during inhibition of angiotensin II

Renal blood flow (RBF) was measured with a noncannulating electromagnetic flow transducer in anesthetized rats which had been maintained for 3-5 wk on low, normal, or high salt plus deoxycorticosterone diets. After base-line observations, one of two dissimilar inhibitors of the renin-angiotensin system, angiotensin I converting enzyme inhibitor SQ 20881 or the structural analogue [Sar1,Ala8]angiotensin II was administered intravenously. The employed doses of SQ 20881 and [Sar1,Ala8]angiotensin II effectively inhibited the pressor and renal vasoconstrictor responses induced by exogenous angiotensin I and II, respectively, in each dietary group. Both inhibitors vasodilated kidneys in salt-restricted rats; however, neither affected base-line renal hemodynamics in salt-loaded rats. Pressure-flow relationships were evaluated by clamping the aorta to reduce renal perfusion pressure. Renal blood flow was autoregulated between 100 and 140 mmHg with the same efficiency before and during inhibition of angiotensin II in each dietary group. These data indicate that angiotensin II modifies base-line RBF and renal vascular resistance and are consistent with the view that the renin-angiotensin system is not an essential mechanism responsible for autoregulation of RBF in the rat.     

Determination of bone mineral content using CT scanning

The usefulness and accuracy of CT scanning in the determination of bone mineral content is studied. The radius in 31 patients of both sexes and varying ages was examined using both the Norland-Cameron bone mineral analyzer and the CT scanner. There was reasonably good correlation (r=.72). Ten cadaver bones were then examined with CT scanning and were sent to the laboratory for calcium determination. These results indicate excellent correlation (r=.97). It is concluded that CT scanning represents the only practical and accurate in vivo method of bone mineral content determination.     

Relationship of cervical and abdominal vagal activity to lower esophageal sphincter function

The purpose of this study was to compare the effects of electrical stimulation of the abdominal and cervical portions of the vagus on lower esophageal sphincter (LES) pressure in the anesthetized opossum. Unilateral or bilateral abdominal vagotomy gave no significant change in basal LES pressure or in the sphincteric response to swallowing. Electrical stimulation of the peripheral end of the sectioned cervical vagus gave a frequency-related decrease in LES pressure with a maximum reduction of 93.5 +/- 2.5% at 10 HZ, 10 V. Stimulation of the central end of the cervical vagus increased LES pressure, with a maximum response of 34.0 +/- 1.9 mm Hg. Neither peripheral nor central stimulation of the sectioned abdominal vagus had significant effect on LES pressure (P greater than 0.05). Additionally, LES relaxation in response to swallowing or cervical vagal stimulation was intact after bilateral abdominal vagotomy. These studies suggest that whereas the cervical portion of the vagus mediates inhibitory and excitatory changes in LES pressure, the abdominal vagus has no demonstrable role in the control of LES function.     

Comparison of rest/exercise ECG, thallium-201 scans and radionuclide angiography in patients with suspected coronary artery disease

The results of rest and exercise ECG, 201Tl myocardial perfusion imaging and equilibrium radionuclide angiography were analyzed in 71 consecutive patients referred for diagnosis or evaluation of coronary artery disease (CAD). In 45 patients the diagnosis was established either by catheterization or typical history. In this group the overall sensitivity for rest/exercise ECG was 66%, for 201Tl scans 74%, for both combined 79% and for the ejection fraction response to exercise determined by radionuclide angiography 97%. If only the exercise response was considered, the corresponding sensitivity values were 58% (ECG), 50% (201Tl scans), 71% (ECG + 201Tl) and 97% (radionuclide angiography). The specificity for coronary artery disease was determined to be 71% for ECG, 86% for 201Tl scans and 42% for radionuclide angiography. All patients with false-positive results by radionuclide angiography had cardiomyopathies, thus this test has a high specificity for left ventricular dysfunction rather than for CAD alone. Criteria developed from the analysis of the test results in the 45 patients with definite diagnoses were then applied to the evaluation of 26 additional patients with atypical chest pain. A diagnosis could be made in all but 5 of them and radionuclide angiography was again the single most reliable test. Based on this study a new approach for the noninvasive evaluation of patients with suspected coronary artery disease is proposed.